Cancer Drugs Aim at More Targets

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Cancer Drugs Aim at More Targets

NEW YORK – Last year, the big news in cancer therapy was Avastin, a colorectal cancer drug that extends life by an average of five months. This year, scientists are looking hard at the "children" of Avastin, drugs that are based on the same principle but have additional bells and whistles.

Avastin works by cutting off blood supply to tumors, a process known as anti-angiogenesis. New drugs under development, to be discussed at the year's biggest cancer conference this weekend, do that, but also home in on proteins that help cancer cells grow.

Moreover, they come in the form of pills, whereas most cancer drugs are delivered intravenously.

"These drugs represent the next generation of anti-angiogenesis drugs beyond Avastin," said William Li, president and medical director of the Angiogenesis Foundation, a non-profit institution based in Cambridge, Massachusetts. "If chemotherapy is like a dirty bomb and Avastin like a smart bomb, then the new therapies are more like cluster bombs that have multiple targets."

Data from mid-stage clinical trials of these drugs will be presented this weekend at the annual meeting of the American Society of Clinical Oncology in New Orleans, and the results are expected to show promise.

Pfizer will present mid-stage data on a drug with the working title SU11248. It hits four targets, including a protein known as VEGF, which is heavily involved in the process of angiogenesis and is targeted also by Avastin. The drug also targets KiT, which is hit by Novartis's successful drug Gleevec; and FLT-3, which is found on both cancer cells and tumor blood vessels.

While more may prove better in some ways, cancer specialists point out that the more targets that are hit the more likely the drug is to cause side effects and toxicity. But George Demetri, director of the Sarcoma Center at the Dana Farber Cancer Institute, said the side effects are not intolerable.

"Compared to chemotherapy they are still very manageable," he said.

Bayer and Onyx Pharmaceuticals are co-developing a drug, BAY 43-9006 that hits a new target known as RaF kinase, an enzyme that acts as a control switch for the RaF gene, which helps control tumor growth. It also targets VEGF, which is considered one of the main proteins involved with blood vessel growth.

It isn't clear to scientists, however, which target is responsible for promising results in early trials, which is one of the disadvantages of all targeted therapies.

Genentech will present data from a mid-stage trial combining Avastin with Tarceva, a drug it is developing with OSI Pharmaceuticals. Unlike the others, these are separate drugs that hit two different targets.

All three combinations are being developed for kidney cancer, known to be packed with blood vessels that rely heavily on VEGF to flow. The trials are in renal cell carcinoma, which accounts for about 85 percent of all kidney cancer, a condition that affects about 31,000 patients a year.

Novartis and Schering are co-developing a drug for colorectal cancer, PTK 787, that turns off all the VEGF receptors, meaning no VEGF signal can bind to them. Avastin blocks just one of the five VEGF signals that bind to the three receptors.

"Our expectation is that we will be able to have a more complete blockade of the angiogenesis process which may result in superior efficacy compared to Avastin," said David Guy, vice president of global strategic marketing, oncology, for Schering.